This invention relates to stabilized azithromycin compositions, methods of preparing stabilized azithromycin compositions, pharmaceutical formulations containing the stabilized azithromycin compositions and methods of making such formulations.
The first of the macrolide antibiotics, erythromycin, was discovered in 1952 among the metabolic products of Streptomyces erythreus. Erythromycin is most effective against Gram-positive bacteria. Erythromycin has low acid stability which reduces its oral bioavailability and necessitates enteric coating of the drug.
Azithromycin, (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-xcex1-L-ribo-hexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethyl amino)-xcex2-D-xylo-hexopyranosyl]oxy]-1-Oxa-6-azacyclopentadecan-15-one, may be considered a second generation macrolide antibiotic.
Azithromycin is subject to degradation that can occur during manufacture and storage. In particular, the amine group of azithromycin is susceptible to oxidation. For example, azithromycin is susceptible to degradation if exposed to elevated temperatures and/or air during manufacturing processes, including processes of formulating pharmaceutical dosage forms of azithromycin. This could cause the drug product to deviate from regulatory purity requirements even before the product reaches doctors and patients. Additionally, once formulated, azithromycin has a tendency to degrade under normal storage conditions, which may result in an unacceptable level of impurities at the time of administration.
Thus, there exists a need for improved azithromycin compositions and methods of manufacturing such compositions in which the tendency for degradation of the azithromycin is reduced, resulting in azithromycin compositions with a higher degree of purity.